Dental Research and Management (ISSN: 2572-6978)

Editorial :

Selective Killing Natural Products and Drugs in Oral Cancer Treatments

Hsueh-Wei Chang


Most  cancer  drugs  are  effective  to  kill  cancer  cells  but  also  harm  normal  cells.  Drugs and natural products with the selective killing effect may be helpful to solve this problem. The side effects of many anticancer drugs are partly derived from its damage to both  cancer and normal cells without selection. This problem raises the need of anticancer drug discovery with the selective killing effect. Recently,  several  drugs  with  reactive  oxygen  species  (ROS)-modulating  effects  have reported to be selective killing against cancer cells [1,2]. It may be partly explained by  the  concept  that  normal  cells  tolerate  a  certain  level  of  drugs-induced  ROS  but  it  may  exceed  the  ROS  threshold  in  cancer  cells,  leading  to  cancer  cell  death  but  less  harmful to normal cells [3,4].

Many  ROS-generating  natural  products  and  drugs  had  been  reported  but  their  selective  killing  effects  were  sometimes  not  investigated  [5-7].  It  was  warranted  for  further investigation about its possible selective killing effects. In contrast, it is noted that  the  ROS-generating  natural  products  and  drugs  are  not  always  displaying  the  selective killing effect.Some antioxidants were reported to have dual roles for cell survival and cell killing
in respective to different dosages [8], i.e., it displayed the survival effects at physiologic doses and the deleterious effects at high doses. In case of grape seed extracts, the famous natural  products  with  an  antioxidant  property,  it  was  found  to  be  healthy  to  normal  oral cells but inhibited the proliferation of oral cancer Ca9-22 cells at high doses [9].

Accordingly, the selective killing effects of antioxidants may be dose-dependent and or cancer cell type-dependent. Thus, the drugs and natural products with suitable ROS modulating effect may be  the anticancer drug candidates with selective killing.

Funding Support

This  work  was  supported  by  funds  of  the  Ministry  of  Science  and  Technology  (MOST  104-2320-B-037-013-MY3),  the  Kaohsiung  Medical  University  “Aim  for  the  Top  Universities  Grant,  grant  No.  KMU-TP103A33”,  the  Health  and  welfare  surcharge of tobacco products, the Ministry of Health and Welfare, Taiwan, Republic of China (MOHW104-TDU-B-212-124-003).


1. Chiu  CC,  Haung  JW,  Chang  FR,  Huang  KJ,  Huang  HM,  etal.  Golden  berry-derived  4beta-hydroxywithanolide E for selectively killing oral cancer cells by generating ros, DNA damage, and apoptotic pathways (2013) PLoS One 8:e64739.
2.    Suzuki-Karasaki  Y,  Suzuki-Karasaki  M,  Uchida  M,  Ochiai  T.  Depolarization  controls  trail-sensitization and tumor-selective killing of cancer cells: Crosstalk with ros (2014) Front Oncol 4:128.
3.    Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ros-mediated mechanisms: A radical therapeutic approach?  (2009) Nat Rev Drug Discov 8:579-91.
4.    Gupte A, Mumper RJ. Elevated copper and oxidative stress in cancer cells as a target for cancer treatment (2009) Cancer Treat Rev 35:32-46.
5.    Yen YH, Farooqi AA, Li KT, Butt G, Tang JY, et al. Methanolic extracts of Solieria robusta inhibits proliferation  of  oral  cancer  ca9-22  cells  via  apoptosis  and  oxidative  stress  (2014)  Molecules 19:18721-18732.
6.    Yeh CC, Tseng CN, Yang JI, Huang HW, Fang Y, etal. Antiproliferation and induction of apoptosis in  ca9-22  oral  cancer  cells  by  ethanolic  extract  of  Gracilaria  tenuistipitata  (2012)  Molecules 17:10916-10927.
7. Yen CY, Chiu CC, Haung RW, Yeh CC, Huang KJ, etal. Antiproliferativeeffects of goniothalamin on ca9-22 oral cancer cells through apoptosis; DNA damage and ros induction (2012) Mutat Res 747:253-258.
8.    Bouayed J, Bohn T. Exogenous antioxidants - double-edged swords in cellular redox state: Health beneficial effects at physiologic doses
versus deleterious effects at high doses (2010) Oxid Med Cell Longev 3:228-237.
9.    Yen CY, Hou MF, Yang ZW, Tang JY, Li KT, et al. Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis,
oxidative stress, and DNA damage (2015) BMC Complement Altern Med 15:94.


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