Phytochemicals offer new clues for breast cancer treatment

Extracts from plants ranging from cabbages to figs are offering new clues for prevention or improvement of breast cancer treatment. Several plant chemicals or phytochemicals are being tested for their ability to arrest the growth of breast cancer cells in animal models, according to scientists attending an international conference on cancer research in New Delhi.

The three-day conference on 'Current Advances in Radiobiology, Stem Cells and Cancer Research' (February 19-21, 2015) heard about the effects of three plant-based compounds — the root bark of Ailanthus excelsa Roxb or Indian Tree of Heaven, cabbage (Brassica oleracea) and fig (Ficus carica) — on breast cancer cells.

Some plant-based drugs such as taxol, vincristine and vinblastin are in use for breast cancer treatment. “Most drugs in the market are derived from phytochemicals present in of our diets. These are safe and protect against cancers in ways that are still not known," according to Rana Singh, professor at the cancer biology lab of New Delhi-based Jawaharlal Nehru University's school of life sciences, organisers of the conference.

“In epithelial cancers, including breast cancer, several stages — initiation, promotion and progression — lead to full-blown cancer. These stages provide a window of opportunity to diagnose cancer at an early stage and treat it,” Rana told Nature India. Phytochemicals may work for a particular stage, for example, to inhibit the crucial p53 gene mutation that causes cancer, or repair the mutated gene, he said.

A group of chemicals called flavanoids help reduce the strong effect of oestrogen that influences breast cancer, while others target key pathways such as ‘apopotosis’ or cell death, and still others prevent ‘angiogenesis’ or the process of formation of new blood vessels which triggers dormant cancers.

New phytochemical leads

Scientists from the National Centre for Cell Science (NCCS), Pune, have attempted to target breast cancer stem cells with a substance they isolated from the root bark of Ailanthus excelsa Roxb. “Regardless of upcoming chemotherapeutic approaches to combat breast cancer, tumor relapse and metastasis remain largely elusive problems in combating the disease,” their report said.

Their focus was a group of cells within the cancerous tissue, known as cancer stem-like cells (CSC), which act like stem cells and reproduce by themselves, thus sustaining the cancer. CSCs are associated with aspects of the disease such as metastasis, relapse and multi-drug resistance.

They tested the compound, Ailanthus excelsa chloroform extract-1 (AECHL-1), in two breast cancer cell lines. AECHL-1 brought about considerable decrease in CSCs, as well as in ‘mammopshere’ or a clump of mammary gland cells. AECXHL-1 also reduced the amount of a key protein ‘β-catenin’ whose over-expression is linked to several cancers, including malignant breast cancer.

The study lays the “groundwork for further therapeutic applications of this novel compound,” their report said.

Similarly, researchers from JNU’s school of environmental sciences tested an extract from fig or F. carica for its anti-oxidant and anti-cancer effects in breast carcinoma. The fruit contains a range of phytochemicals, from terpeniods, tannins, phenols, flavanoids, glycosides, saponins, and phytosterols. It especially contains considerable amounts of phenolics and anti-oxidants.

The extract inhibited the proliferation and colony-forming ability of the breast cancer cells, and “induced a significant amount of cell death in breast carcinoma cells. The extract of F. carica has a considerable amount of anti-oxidants and anti-cancer properties and, hence, the fruit may be used as chemopreventive agent,” the JNU team reported.

Another plant extract offering a promising lead is cabbage ( B. oleracea ). Biochemists from the Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, tested an extract of B. oleracea , combined with Vitamin D3, selenium and proline, for its anti-cancer and toxicological effects in breast cancer cell lines.

Like all pungent plants such as mustard and horseradish, B. oleracea contains glucosinolates, reported to have anti-cancer therapeutic effects. The Nagpur scientists tested hot and cold cabbage extracts on groups of rats to check what doses worked best. The results helped the scientists decide the concentration of cabbage extract required to prepare an effective nutrient medium to supplement the drug treatment and prevent metastasis of breast cancer to bone. “These results signify the role of nutrient therapy to regress the metastasis of the breast tumour to the bone,” they reported.

Algorithm to identify plant compounds

Scientists also reported other approaches to combat breast cancer. A team from Delhi University’s department of environmental studies teamed up with biophysicists from the All India Institute of Medical Sciences (AIIMS), Delhi to come up with a computer algorithm to identify plant compounds that could be useful in treating breast cancer.

The scientists studied protein-ligand interactions involving a group of immune molecules called interleukins (IL) as targets. They focused on IL-6 and IL-12 which have been suggested to play a significant role in the advancement of breast cancer, and whose expression in patients has also been found to be 55-65 fold higher compared to healthy volunteers.

To identify a natural inhibitor having high affinity for IL-6 and IL-12, the scientists analysed five different plant compounds of different species such as genistein (isoflavone), quercetin (flavonol), resveratrol (phenol), xanthatin (sesquiterpenoids) and rosmanol (phenolic terpenes). Further tests on such multi-targeted compounds will help unravel the molecular mechanism behind their action and their ability to prevent disease severity.

Scientists are reporting significant benefits of combining phytochemicals with chemotherapy, either as complementary or adjuvant treatment, Rana said. They are also finding use in different treatment regimens that combine chemotherapy, radiation treatment and surgery.

Phytochemicals are relatively less toxic and can work at all stages, unlike chemical drugs that only kill the cancer cells. But they also have a problem of poor selectivity, affecting normal cells too in addition to cancer cells.

Most research on them is still at the preclinical stage. “We need some planned trials with appropriate patient selection or people identified to be at high risk, to take the leads further," Rana said.