Effect of Paclitaxel and Carboplatin on Cancer H520 Cells
prior to paclitaxel/carboplatin treatment (Table 3, Fig. 1). Pre-
treatment with an antioxidant mixture enhanced the level of
apoptosis induced by paclitaxel/carboplatin combination con-
sistently (Table 3, Fig. 1). When the mixture was added im-
mediately before paclitaxel, the level of apoptosis rose to
70.11% (Fig. 1d), as compared to maximum apoptosis (54.3%)
(Fig. 1c) observed with a paclitaxel/carboplatin combination
(p ϭ 0.022). However, when the mixture was added 24 hours
prior to paclitaxel, the level of apoptosis significantly rose to
89.15% (Fig. 1e) (p ϭ 0.014).
These observations suggest that antioxidant vitamins/provi-
tamins with paclitaxel and carboplatin therapy may have utility
in the treatment of lung cancer. Pretreatment with antioxidant
mixture followed by paclitaxel and carboplatin exhibited
greater than additive effect indicating a potential synergistic
combination for NSCLC. This combination thus may provide
more efficacious treatment of non-small cell lung cancer.
The results of our study show that the antioxidant vitamins/
provitamins induce cytotoxicity by themselves in H520 cells.
These agents also enhance the level of apoptosis induced by the
combination of paclitaxel and carboplatin. Thus it seems that
the response rate to this chemotherapy regimen in the manage-
ment of NSCLC might be improved with the addition of an
antioxidant mixture. A higher level of apoptosis has been found
to be associated with longer survival in NSCLC [21]. The
mechanism of action of these agents in the induction of apo-
ptosis is not very clear. Further studies need to be carried out to
investigate this aspect.
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5. Prasad KN, Kumar A, Kochupillai V, Cole WC: High doses of
multiple antioxidant vitamins: essential ingredients in improving
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6. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study
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Another rationale for using antioxidants in combination
with chemotherapeutic agents involves the possible reduction
of toxicity of several chemotherapeutic agents on normal cells
by these agents [22–35]. The antioxidant mixture is more
effective than the individual components in protecting normal
cells against radiation damage [35]. This particular aspect,
however, was not evaluated in the present study.
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CONCLUSION
An antioxidant vitamins/provitamin mixture appears to be
potentially useful in the management of NSCLC. The mixture
enhances the apoptosis induced by standard chemotherapeutic
agents employed for the management of NSCLC, i.e., pacli-
taxel and carboplatin. Since the mechanism of the action of the
components of this antioxidant mixture is not entirely clear, this
needs to be studied; also, there is a need to initiate clinical trials
to determine the in vivo effect of these antioxidants in conjunc-
tion with chemotherapy in the management of human cancers.
15. Yang Y, Vacchio MS, Ashwell JD: 9-cis-retinoic acid inhibits
activation-driven T-cell apoptosis: implications for retinoid X re-
ceptor involvement in thymocyte development. Proc Natl Acad Sci
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16. Huizing MT, Keung AC, Rosing H, Vander Kuij V, Ten Bokkel
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JH: Pharmacokinetics of paclitaxel and metabolites in a random-
ized comparative study in platinum pretreated ovarian cancer pa-
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