原文网址：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359575/
发表在Scientific Reports 影响因子4.259
部分文章搬运如下
Venom from Cuban Blue Scorpion has tumor activating effect in hepatocellular carcinomaCatia
Giovannini,a,1,2 Michele Baglioni,1 Marco Baron Toaldo,3 Matteo Cescon,4 Luigi Bolondi,1,2 and Laura
Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC.
Complementary and alternative medicine (CAM) is the term for diverse medical and health care systems, practices and products that are not part of conventional medical care1. These forms of treatment are used in addition to (complementary) or instead of (alternative) standard treatments2. The 2007 National Health Interview Survey reported that about 4 out of 10 adults use a CAM therapy, naming natural products and deep breathing exercises as the most commonly used treatments. Particularly CAM arouses the interest of cancer patients3,4,5 as supportive measures that control symptoms, enhance well-being, and contribute to their overall care. Cancer patients considering complementary and alternative therapies should discuss this decision with their oncologists because some CAM may interfere with their standard treatment or may be harmful when used with conventional therapy. Often, patients taking CAM do not inform oncologists who are not able to regard side effects of CAM substance as reason of adverse effects diagnosed in patients. CAM therapies should be evaluated with the same long and careful research process used for standard treatments. Standard cancer treatments are studied for safety and effectiveness through an intense scientific process that includes clinical trials with large numbers of patients. The National Cancer Institute (NCI) and the National Center for Complementary and Integrative Health (NCCIH) have sponsored various clinical trials that test CAM treatments and therapies in people. Some studies focused on the effects of complementary approaches used in addition to conventional treatments, and some compare alternative therapies with conventional treatments (Cancer CAM Clinical Trials-OCCAM). A small number of CAM therapies, originally considered purely alternative approaches, are finding a place in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) in November 1997, acupuncture has been found out to be effective in the management of chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery6. However, it is not possible to evaluate all the CAM treatments due to high cost and consequently, in most cases, the side effects are unknown. Thus, CAM in oncology is still a sensitive issue due to side effects and interactions with conventional treatments and to the enormous economic impact7,8. Moreover, patients may focus on alternative treatments and omit conventional therapy thus decreasing the possibility of cancer remission9,10.
The scorpion venom is considered a natural source for cancer therapy11. In particular Escozul, (Labiofam) is a commercial product made from the venom of Rhopalurus junceus, a rare blue scorpion found only in Cuba, is considered as a potential novel cancer therapeutic12. In March 2011, the Cuban company Labiofam registered the product in homeopathic formula called Vidatox 30-CH that is an alcoholic solution at 33% resulting from five low molecular weight peptides extracted from the blue scorpion venom. According to Gonzalez, Vidatox was tested on more than 10,000 cancer patients with “positive results” ranging from an “improved quality of life” to a “slowing of tumor growth” (http://vidatoxromania.ro/en/what-is-vidatox/) (http://www.bt.com.bn/science-technology/2010/10/29/cuba-release-new-cancer-drug). There are no data from controlled clinical studies neither for Escozul nor for Vidatox 30-CH in refereed journals. The available information derived from interviews with patients involved or provided within the sites of alternative therapies. Essentially, scientific evidences about the biological activity of Vidatox in cancer cells are missing.
Here we evaluated the effects of Vidatox in hepatocellular carcinoma (HCC), the second leading cause of cancer mortality worldwide. We focused on HCC because no data on Vidatox efficacy are actually available in orthotopic models of HCC and because DEN-induced rat HCC recapitulates many molecular features of human HCC, as previously reported by our group. In addition, the effects of CAM could be particularly relevant in an organ involved in both drug metabolism and coagulation such as the liver.
We showed that Vidatox induces cancer cells proliferation both in vitro and in vivo whereas sorafenib induced apoptosis was unaffected by Vidatox treatment in HepG2 cells. We also found that Vidatox treated HCC cells have a high level of penetration through the matrigel-coated membrane compared with control cells.
Go to:ResultsVidatox induces hepatocellular carcinoma proliferation and invasion
Many cancer therapeutic agents activate the p53 pathway to induce growth arrest and apoptosis therefore, p53 status is crucial to the response of HCC to some therapies13. Since P53 mutations are not described in HepG2 and Snu449 cell lines, we employed them as in vitro models to analyze the effects of Vidatox on hepatocellular carcinoma.
To evaluate the effect of Vidatox on cell cycle regulation we firstly performed cell cycle analysis by flow cytometry. Vidatox significantly reduced cell cycle arrest at the G1/S phase transition (Fig. 1A). Then, we determined the expression levels of Cyclin D1, p53, p21, pRb, phospho-pRb, p16, p27, Akt, Erk1/2, p38 and k-Ras after Vidatox treatment for 24h.
发表在Scientific Reports 影响因子4.259
部分文章搬运如下
Venom from Cuban Blue Scorpion has tumor activating effect in hepatocellular carcinomaCatia
Giovannini,a,1,2 Michele Baglioni,1 Marco Baron Toaldo,3 Matteo Cescon,4 Luigi Bolondi,1,2 and Laura
Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC.
Complementary and alternative medicine (CAM) is the term for diverse medical and health care systems, practices and products that are not part of conventional medical care1. These forms of treatment are used in addition to (complementary) or instead of (alternative) standard treatments2. The 2007 National Health Interview Survey reported that about 4 out of 10 adults use a CAM therapy, naming natural products and deep breathing exercises as the most commonly used treatments. Particularly CAM arouses the interest of cancer patients3,4,5 as supportive measures that control symptoms, enhance well-being, and contribute to their overall care. Cancer patients considering complementary and alternative therapies should discuss this decision with their oncologists because some CAM may interfere with their standard treatment or may be harmful when used with conventional therapy. Often, patients taking CAM do not inform oncologists who are not able to regard side effects of CAM substance as reason of adverse effects diagnosed in patients. CAM therapies should be evaluated with the same long and careful research process used for standard treatments. Standard cancer treatments are studied for safety and effectiveness through an intense scientific process that includes clinical trials with large numbers of patients. The National Cancer Institute (NCI) and the National Center for Complementary and Integrative Health (NCCIH) have sponsored various clinical trials that test CAM treatments and therapies in people. Some studies focused on the effects of complementary approaches used in addition to conventional treatments, and some compare alternative therapies with conventional treatments (Cancer CAM Clinical Trials-OCCAM). A small number of CAM therapies, originally considered purely alternative approaches, are finding a place in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) in November 1997, acupuncture has been found out to be effective in the management of chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery6. However, it is not possible to evaluate all the CAM treatments due to high cost and consequently, in most cases, the side effects are unknown. Thus, CAM in oncology is still a sensitive issue due to side effects and interactions with conventional treatments and to the enormous economic impact7,8. Moreover, patients may focus on alternative treatments and omit conventional therapy thus decreasing the possibility of cancer remission9,10.
The scorpion venom is considered a natural source for cancer therapy11. In particular Escozul, (Labiofam) is a commercial product made from the venom of Rhopalurus junceus, a rare blue scorpion found only in Cuba, is considered as a potential novel cancer therapeutic12. In March 2011, the Cuban company Labiofam registered the product in homeopathic formula called Vidatox 30-CH that is an alcoholic solution at 33% resulting from five low molecular weight peptides extracted from the blue scorpion venom. According to Gonzalez, Vidatox was tested on more than 10,000 cancer patients with “positive results” ranging from an “improved quality of life” to a “slowing of tumor growth” (http://vidatoxromania.ro/en/what-is-vidatox/) (http://www.bt.com.bn/science-technology/2010/10/29/cuba-release-new-cancer-drug). There are no data from controlled clinical studies neither for Escozul nor for Vidatox 30-CH in refereed journals. The available information derived from interviews with patients involved or provided within the sites of alternative therapies. Essentially, scientific evidences about the biological activity of Vidatox in cancer cells are missing.
Here we evaluated the effects of Vidatox in hepatocellular carcinoma (HCC), the second leading cause of cancer mortality worldwide. We focused on HCC because no data on Vidatox efficacy are actually available in orthotopic models of HCC and because DEN-induced rat HCC recapitulates many molecular features of human HCC, as previously reported by our group. In addition, the effects of CAM could be particularly relevant in an organ involved in both drug metabolism and coagulation such as the liver.
We showed that Vidatox induces cancer cells proliferation both in vitro and in vivo whereas sorafenib induced apoptosis was unaffected by Vidatox treatment in HepG2 cells. We also found that Vidatox treated HCC cells have a high level of penetration through the matrigel-coated membrane compared with control cells.
Go to:ResultsVidatox induces hepatocellular carcinoma proliferation and invasion
Many cancer therapeutic agents activate the p53 pathway to induce growth arrest and apoptosis therefore, p53 status is crucial to the response of HCC to some therapies13. Since P53 mutations are not described in HepG2 and Snu449 cell lines, we employed them as in vitro models to analyze the effects of Vidatox on hepatocellular carcinoma.
To evaluate the effect of Vidatox on cell cycle regulation we firstly performed cell cycle analysis by flow cytometry. Vidatox significantly reduced cell cycle arrest at the G1/S phase transition (Fig. 1A). Then, we determined the expression levels of Cyclin D1, p53, p21, pRb, phospho-pRb, p16, p27, Akt, Erk1/2, p38 and k-Ras after Vidatox treatment for 24h.
