August 22, 2018

The future of breast cancer therapy: Light-exposed plant extracts

Picture1   By: Roselle Eloise Bunayog

 

For Dr. Sonia Jacinto, a professor at the Institute of Biology in the University of the Philippines–Diliman, if a natural extract displays no activity against cancer, it makes its way onto the shelves. This has been the case for two local plant extracts—kulasi and akleng parang—when they were initially tested back in 2015. But in mid–2016, these two extracts were suddenly brought back into the limelight.

It was exciting to hear Rigo Villacorta, an undergraduate student at the Institute of Biology, present his discovery: when exposed to a broadband light, the kulasi and akleng parang extracts can cause the premature death of breast cancer cells. They even leave the normal cells unharmed or minimally damaged.

“This is something that I’ve never experienced before,” says Jacinto, who specializes in searching for natural products against cancer. “We didn’t know that a simple zap of light on the extracts can activate it and can go so far as killing cancer cells or at least limit its growth.”

Commonly known as kulasi, tabao or bolali in Negros Occidental, Lumnitzera racemosa is a tree found along tidal creeks and muddy substrates of mangroves1. On the other hand, akleng parang, or Albizia procera, is a tree planted by farmers for rehabilitation of eroded and degraded soils2. Neither species have shown remarkable medicinal activity against cancer until now.

The idea was laid out earlier that year when Dr. Giovanni Tapang, a professor at the National Institute of Physics, UP Diliman, approached Jacinto to collaborate on a study. “I had a meeting with my advisees and I asked them who wanted to work with Dr. Tapang,” she says, explaining that the team might face a challenge since they’ll be injecting a bit of physics into their work. This was the start of a budding partnership between biology and physics in order to combat cancer.

 A new light

The search for new and more effective treatments against breast cancer has been a frantic race among research groups and pharmaceutical companies for decades. The unique approach developed by Dr. Jacinto’s team shows much promise. It involves the use of photodynamic therapy (PDT), a process where light is used to activate plant extracts. In their study, the team exposed the plant extracts to red broadband light. The light provides sufficient energy to excite the photosensitizer, a molecule that induces chemical change, found within the extracts. In turn, the photosensitizer becomes activated, from ground state to its excited state. When it returns to its ground state, it releases excess energy to oxygen generating free radicals3.

“Apparently, according to literature, the activation of reactive oxygen species (ROS) or free radicals could start a chain of reaction,” Jacinto says, “destroying nucleic acids [and] proteins of different cells until they eventually die.”

A study published by the Philippine Cancer Society in 20154 showed that breast cancer has the highest mortality rate of all types of cancer among women, with 23% of patients dying within a certain length of time after diagnosis. The majority are seemingly unaware that breast cancer is curable if detected at its early stages. At present, scientists are turning their heads to natural therapies, with the vision of helping millions of affected Filipinos combat the debilitating disease.

PDT might offer an unparalleled cure to cancer. Unlike chemotherapy, radiotherapy and surgery, PDT-treated plant extracts will most probably not cause long-term side effects to patients, such as hair loss, fatigue and nausea. It is also non-invasive, requires shorter treatment time and has lower cost.

The wonder in the in-vitro results, as published in Asia Pacific Journal of Tropical Biomedicine5, is two-fold: First, L. racemosa and A. procera crude plant extracts remain harmless on breast cancer cells. However, a short exposure to low intensity light revealed their destructive effect. The study showed L. racemosa and A. procera had inhibitory values close to doxorubicin, a known chemotherapy medication. On the other hand, another tested plant extract, Cananga odorata or ilang-ilang was not activated when exposed to light.

“The fact that not all plant extracts behave this way suggests that the presence or abundance of photosensitizing molecules is a distinctive property of some plants such as L. racemosa and A. procera,” Villacorta explains in their paper. This result indicates that not all plants possess these potential sensitizers that become activated when hit by broadband light.

Second, the selective attack of the plant extracts against the malignant cells opens a portal for further exploration. This is because the production of free radicals causes irreversible damage to any type of cell—whether a normal cell or a cancer cell. Dr. Jacinto attributes the discriminatory phenomenon to the possible difference of molecules and metabolism between the normal and malignant cells.

“It was exciting to see that there was selectivity on the cancer cells than the normal ones. Hopefully we can follow up on that,” Jacinto adds.

High hopes

While the results are promising, Jacinto says there’s still a long way to go before PDT can be used to treat cancer in humans. The next challenge is to conduct in vivo experiments on animals followed by clinical studies.

“I see a disadvantage [in PDT] since it cannot kill cancer cells inside the body,” Jacinto explains, adding that light cannot penetrate the deeper tissues resulting to treatment of tumors or lesions found only in shallower or surface tissues.

One critical factor to consider in the next steps is the light wavelength. It must be long enough to penetrate deeply into the tissues, but short enough to provide energy to excite oxygen and produce a substantial yield of ROS.

The study also calls attention to the country’s uncharted plant biodiversity. The effort to develop alternative cures, in the present, is attracting not just scientists, but also government officials, who are convinced that natural products have more to offer. Whether it benefits patients or not remains, however, a matter of debate among medical professionals.

“It would be exciting to discover plant extracts which by themselves have no activity on cancer cells,” the authors add in their paper,“ but with exposure to light can turn to photosensitizing agents which are strongly toxic to malignant cells.”

Perhaps more importantly, this study could draw in researchers from other fields with a fresh perspective. Hopefully, PDT will open doors to much wider applications, with the hope of treating other diseases in the future.

 

References:

  1. Hanum, F. and Van der Maesen, L.J.G. (1997) PROSEA : Plant Resources of South-East Asia 11, Auxiliary Plants. LIPI Press, Jakarta, Indonesia
  2. Southeast Asian Fisheries Development Center Aquaculture Department, Aquaculture (2004) Handbook of Mangroves in the Philippines–Panay
  3. Dennis, E.J. et al. (2003) Photodynamic therapy for cancer. Nature Publishing Group
  4. Laudico, A. V. et al. (2015) 2015 Philippine Cancer Facts and Estimates. Philippine Cancer Society
  5. Villacorta, R. et al. (2017) Plant extracts as natural photosensitizers in photodynamic therapy: in vitro activity against human mammary adenocarcinoma MCF-7 cells. Asian Pacific Journal of Tropical Biomedicine; 2017 7(4): 358–366

This article was written by Ms. Roselle Eloise Bunayog, a BS Biology graduate of UP Manila, and edited by Dr. Lillian Jennifer Rodriguez, a faculty member of the UP Institute of Biology.