In this paper we have explored how cancer cell line U87MG responds to drug penicillamine (PA) with reciprocal enantiomeric identities (i.e.l, d-forms). As nano-conjugation leads to amplification of chirality, cellular response to respective chiral forms is studied in the presence and absence of nano-conjugation. The l, d-forms of the drug (penicillamine) and their silver nanoparticle conjugated forms are used and characterized by circular dichroism and fourier transform infrared spectroscopy. We report that cells discriminate between the chiral forms through various mechanisms e.g. by altering mitochondrial membrane potential and selected elements of the caspase pathway. The striking feature which we would like to report is that chirality and the amplified chirality induced reciprocal responses may be dissimilar and even reciprocal. The work shows that the cellular response to geometrical chirality is an evolved concept and an amplified chirality by processes like nano-conjugation may be translated into an altered message in the cell. © 2013 The Royal Society of Chemistry.