Researchers at the Pune-based National Centre for Cell Science (NCCS) have been successful in isolating cancer stem cells that cause skin cancer. They have also been able to demonstrate that a compound (Andrographolide) isolated and purified from a herb (Andrographis paniculata) that is found in India to be effective in inhibiting tumour growth — both skin cancer and lung metastasis — in mice. The results were published on July 29, 2016 in the Journal of Investigative Dermatology.
Stem cell properties
“We used multiple markers, including CD133, to isolate and characterise the cancer stem cells in mice and human-specific skin cancer cell lines,” says Dr. Gopal C. Kundu, the senior author of the paper from NCCS. The CD133 positive cells exhibit stem cell properties in various cancers.
To establish that CD133 positive cancer stem cells cause cancer, the researchers injected the cells subcutaneously into mice. All the animals that were injected with CD133 positive cancer stem cells developed skin cancer (melanoma). “The CD133 positive cancer stem cells developed tumour faster than non-cancer stem cells,” he says. The CD133 positive cancer stem cells also produced lung metastasis in a different set of mice that received the cells through intravenous injection.
The drug can eliminate the drug resistant melanoma stem cells that are responsible for tumour relapse and mortality.To test the efficacy of Andrographolide drug candidate, which is being tested in several clinical trials, in inhibiting tumour growth, the researchers injected the compound into the tumour bearing mice. Two different drug dosages were used. The compound at 50 mg/kg body weight dosage was able to inhibit primary tumour (melanoma) growth by about two-third at the end of 24 days. In the case of a higher dosage of 150 mg/kg body weight, the compound was found to inhibit melanoma growth by more than two-third at the end of 24 days.
“Usually patients with malignant skin cancer die because of lung metastasis,” Dr. Kundu says. So the researchers tested the efficacy of the compound in inhibiting lung metastasis by injecting the drug directly into the mice which were previously injected with melanoma cancer stem cells intravenously. “At the end of 27 days, the drug cleared the lung metastasis by about 90 per cent,” he says.
“Substantial experimental evidences from the current study indicate that the compound [Andrographolide] has therapeutic potential for the management of cancer stem-cell mediated melanoma growth and lung metastasis,” Dr. Kundu says.
The ability of the compound to inhibit stem cell mediated-tumour growth and lung metastasis becomes significant as CD133 positive cells show enhanced ability to flush out cancer drugs from inside the cells thereby increasing the probability of tumour relapse. In short, Andrographolide can eliminate the drug resistant CD133 positive melanoma stem cells that are mainly responsible for tumour relapse and mortality.
Further studies are required to test the drug’s ability to inhibit skin cancer and lung metastasis.