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Chinese study describes how cancer cells ‘escape’ programmed suicide during chemotherapy
HONG KONG—After treating several different kinds of human cancer cells with chemicals that initiate apoptosis—or "cell suicide"—scientists at the Chinese University of Hong Kong have discovered an unexpected escape tactic which cancer cells could use to survive chemotherapy.
Publishing their findings in the Jan. 7 edition of the British Journal of Cancer, the scientists believe their work could eventually lead to the development of new therapeutics to prevent the recurrence of cancer.
"We are surprised that cancer cells can reverse a chemical induced dying-process, which is generally assumed to irrevocably commit cells to die," said Prof. Ming-chiu Fung, a senior author of the study. "The current new finding uncovers another possibility that may contribute to cancer recurrence and, therefore, suggests new targets for the therapeutical advancement and drug development to cure cancer."
Apoptosis is a cell suicide program that plays an essential role in body development and homeostasis in multicellular organisms. Because dysfunction in apoptosis can lead to many diseases, such as cancer and autoimmune and neurodegenerative diseases, controlling it is an important strategy for treating these intractable diseases.
Particularly in cancer, inducing apoptosis in cancer cells is the major action of many cancer-fighting drugs, including chemotherapy. However, Fung's team noted that data has shown that cancer can often recur during cycles of chemotherapy treatment.
Hypothesizing that cancer cells may survive after the removal of the cancer-fighting chemical, the scientists applied cytotoxic chemicals to induce cancer cells to undergo apoptosis. Using time-lapse living cell microscopy, the research team discovered that when the cells showed apoptotic landmarks—mitochondrial fragmentation, nuclear condensation and cell shrinkage—they could regain their normal morphology and continue to proliferate after the removal of the chemicals. The scientists further confirmed the initiation of apoptosis on the induced cells by Western blot analysis and biochemical assays for a decisive group of "executioner" proteins called caspases. The results demonstrated that the cancer cells which recovered from induced-apoptosis could divide, Fung says.
"We found that chemical-induced cancer cells could survive even they displayed the morphological and biochemical landmarks of apoptosis," Fung says. "Importantly, however, cells failed to recover only once the nucleus had started to disintegrate—an event that has been known right at the end of the cell suicide process."
The finding could spark new research into what drives this ability and to what extent the reversibility of apoptosis contributes to the survival and division of cancer cells during cycles of anticancer treatment, Fung says.
"Answers to these questions will provide potential new therapeutic targets in our war against cancer," he says, but he adds that because this study was cellular based, the finding needs to be confirmed in animal models and in clinical cases.
The study, Reversibility of apoptosis in cancer cells, was supported by a grant from the University Grants Committee of the Hong Kong Special Administrative Region in China.